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Purpose: To compare the long-term outcomes of recurrent pterygium surgery between three different techniques., Methods: We performed a 15-year follow-up study of a randomized controlled study on surgical management of recurrent pterygium. Group 1 received limbal conjunctival autograft (LCAU); group 2 received intraoperative mitomycin C (MMC) 0.02% for 5 min; and group 3 received combined LCAU + MMC 0.02% for 5 min. Consecutive patients enrolled in the original study (from April 2001 to March 2003) were invited back for a detailed clinical examination to document the long-term outcomes. The main outcome measures included the recurrence rate, residual conjunctival bed status, and complications from any of the surgical methods., Results: Sixty-two patients were recruited in the original study. Eight patients had passed away and 12 patients were uncontactable or not responded. One patient who had bilateral operations refused to return for follow-up and one eye had insufficient data for analysis. Finally, 40 eyes of 40 patients were included for analyses. One eye developed a recurrence over 15 years and none required a tertiary pterygium operation. The patient received LCAU for a temporal recurrent pterygium developed a 2.2-mm recurrence., Conclusions: All three techniques yielded favorable outcomes for patients with recurrent pterygium. The use of LCAU was associated with better cosmetic outcome.

Pterygium is a fibrovascular subepithelial growth of degenerative tissue over the limbus. It is a common condition worldwide that is especially prevalent in tropical countries within the "pterygium belt." Its exact etiology remains to be elucidated; however, it is strongly associated with exposure to ultraviolet light. The high expression levels of tumor protein p53 (TP53) observed in laboratory studies of pterygium seem to contradict the fast-growing nature of its clinical behavior, and TP53 mutations have been suggested. We demonstrated that mouse double minute 2 (MDM2), a TP53-binding protein, contributes to the inhibition of TP53 activity in human pterygium. Thus, disruption of the MDM2-TP53 interaction should attenuate human pterygium cell growth. For primary pterygium, treatment is relatively straightforward and involves surgical excision. To minimize the risk of recurrence, many adjunctive therapies are adopted, including antimetabolites, such as mitomycin C and 5-fluorouracil, amniotic membrane, different variations on conjunctival and/or limbal conjunctival grafts, and other medications such as anti-vascular endothelial growth factor. In the future, MDM2 antagonists may help further lower the recurrence rates after the treatment of pterygium.

Aims: To confirm that mouse double minute 2 (MDM2) could inhibit p53 activity in human pterygium. And to show the disruption of MDM2-p53 interaction could reactive the functions of p53 in pterygium., Method: Pterygium and corresponding conjunctiva tissues were collected for establishment of primary cell lines. Expression patterns of MDM2 and p53 were detected by immunofluorescence. Protein localization of p53 and MDM2, and transcriptional activity of p53 in both untreated and MDM2 antagonist (Nutlin) treated pterygium cells were quantified., Results: In pterygium, p53 was highly expressed in cytoplasm and slightly expressed in the nuclei. MDM2 was localized in the nuclei. A p53 transcriptional regulated target gene, p21, was not expressed in pterygium tissues, suggesting the p53 transcriptional activity was not active in pterygium. After treatment with Nutlin, increased nuclear localization of p53 (4.05%-80.56%) was observed in pterygium cells along with increasing Nutlin dosages (from 0 to 50 μM, p < 0.001). The expression of p21 was increased after Nutlin treatments in pterygium cells (2.49 folds in 20 μM Nutlin treated cells compared to control treated cells, p = 0.012)., Conclusion: We discovered a novel mechanism in pterygium whereby MDM2 suppresses p53 transcriptional activity despite abundant p53 in pterygium. Disruption of MDM2-p53 interaction by Nutlin could be a potential treatment for pterygium., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Purpose: Nutlin is a drug that has been reported to activate p53 in various cell lines. We aim to study the effects of Nutlin in pterygium and compare the effects of Nutlin and mitomycin C (MMC) in pterygium cell lines., Methods: Pterygium samples (n = 3) were collected during surgical excision. Normal conjunctival tissues (n = 3) were collected from another quadrant of the same eye. Cell lines were established, and cells from passages 2 to 5 were used. Pterygium and conjunctival cells were treated with different doses of Nutlin and MMC. Cell proliferation and cell migration were measured., Results: Cell proliferation was reduced by 39-fold after treatment with 50 μM Nutlin. Cell migration was inhibited with increasing dosages of Nutlin (95% and 28% after treating with 2 and 50 μM Nutlin, respectively). Compared with MMC, Nutlin induced more pterygium cell death and less conjunctival cell death at low doses. At 50% lethal dose for pterygium cells, 95% of conjunctival cells survived after Nutlin treatment, whereas only 63% of conjunctival cells survived after MMC treatment. p21 expression was not detectable in MMC-treated pterygium cells but was detectable after Nutlin treatment., Conclusions: In our study, MMC induced cell death in pterygium and conjunctival cell lines, whereas Nutlin had a targeted impact on pterygium cells. Our results implied that MMC inhibited both pterygium cell proliferation and migration through an apoptosis-independent pathway.

Purpose: To evaluate long-term changes in mean keratometry, astigmatism, true net power (TNP), and total corneal refractive power (TCRP) of corneas after primary pterygium excision., Methods: This is a prospective observational series conducted at a tertiary teaching hospital eye center in Hong Kong. A total of 31 eyes of 31 patients with primary pterygium excision were included. Patients with recurrent or double-headed pterygia or a history of corneal scars from previous trauma, infection, or surgery were excluded. Data were collected prospectively at postoperative weeks 1, 4, 12, and month 18., Results: Mean keratometry of the anterior cornea was 44.3 diopters (D) [95% confidence interval (CI): 43.6-44.9 D] at week 1, 44.3 D (95% CI: 43.6-44.9 D, standard error = 0.3) at week 4, 44.3 D (95% CI: 43.7-44.9 D) at week 12, and 44.1 D (95% CI: 43.5-44.7 D) at month 18. Mean astigmatism of the anterior cornea was 1.1 D (95% CI: 0.7-1.4 D), 1.0 D (95% CI: 0.7-1.3 D), 0.9 D (95% CI: 0.6-1.1 D), and 1.0 D (95% CI: 0.7-1.3 D) at postoperative 1, 4, 12 weeks, and 18 months, respectively. Mean keratometry, astigmatism of the anterior and posterior cornea, TNP and TCRP at 2.0-mm, 3.0-mm, 4.0-mm rings and zones remained unchanged on all follow-up visits (P = 1 for all comparisons)., Conclusions: Keratometric values including TNP and TCRP were stable as soon as 1 week after pterygium excision. This information might help clinicians in planning subsequent intraocular surgery that requires biometric assessment for intraocular lens implantation.

Purpose: To evaluate the long-term change in average corneal densities at 18 months after primary pterygium excision with topical adjuvant mitomycin-C application, particularly the relationship between anterior and posterior corneal layer densities., Methods: Prospective observational case series. Patients were imaged with the Pentacam at 18 months after their surgery. Average corneal densities were the primary outcome and were compared with postoperative weeks 1, 4, and 12 data using paired t test., Results: In all, 31 eyes of 31 patients were recruited. Mean age at time of operation was 62.0 ± 9.4 years. Mean best-corrected logarithm of the minimal angle of resolution visual acuity at 18 months was 0.14. The mean total anterior, central, and posterior average corneal densities were 30.6, 25.9, and 20.5 respectively. Compared with postoperative week 1 data, the anterior layer was reduced by 12.7% (P = 0.0144); however, there was no significant change in the central and posterior layers (P = 0.5353 and 0.0858, respectively). Subgroup analyses did not support the use of a 10- to 12-mm annulus as opposed to total-diameter data, and density reduction effect at 18 months from week 12 and week 1 seemed to be stronger in males (P = 0.0074 and 0.0042, respectively)., Conclusions: Anterior corneal scars continued to diminish in density with time. Previous finding of a significant increase in posterior layer density at postoperative week 12 is likely not a result of optical phenomenon caused by a less dense anterior layer. Sex difference in terms of scar remodeling may be present.

Background/aims: To compare the long-term outcomes of primary pterygium surgery with combined conjunctival rotational autograft and mitomycin C (CRA-MMC), mitomycin C alone (MMC) and limbal conjunctival autograft (LCAU)., Methods: The outcomes of primary pterygium excision followed by conjunctival rotational autograft (CRA) combined with intraoperative 0.02% MMC for 5 min (group 1, CRA-MMC, n=61) were compared with historical control groups consisting of, pterygium excision with MMC (group 2, n=47), and, pterygium excision with limbal conjunctival autograft (LCAU) (group 3, n=29). The main outcome measures were recurrence rate and complications., Results: The mean follow-up period was 101±3 months, 138±2 and 137±2 months in the CRA-MMC, MMC and LCAU groups respectively. Recurrence was noted in one patient (1.6%) in the CRA-MMC, 12 patients with MMC (25.5%) and 2 patients with LCAU (6.9%). The difference in recurrence rate between CRA-MMC and MMC was statistically significant (p<0.001). Early postoperative complications included 3 conjunctival cysts (1 from the CRA-MMC, 2 with MMC alone), 2 symblephara (1 in the MMC group, 1 in the LCAU group), and 1 granuloma in the CRA-MMC group., Conclusions: Pterygium excision followed by CRA-MMC or LCAU are effective means of preventing recurrence. The use of CRA-MMC in pterygium excision may be considered for cases where conventional autograft harvesting is contraindicated or when large grafts for double-head pterygium are required., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Purpose: Corneal densitometry is an inherent feature of the Pentacam device. We aim to assess the changes in corneal scar density with serial Scheimpflug images following primary pterygium excision with topical application of mitomycin-C., Methods: We recruited patients who underwent primary, single-headed pterygium excision with topical adjuvant mitomycin-C. Scheimpflug images were taken at postoperative weeks 1, 4, and 12, and all patients received topical corticosteroid and antibiotic treatment for at least 4 weeks postoperatively. Corneal scar densities were generated by the software for analysis. Secondary outcome measures included intraocular pressures and pterygium recurrence at the end of 12 weeks. Changes in corneal densities between weeks 12, 4, and 1 were calculated., Results: We recruited 31 eyes of 31 patients, of whom 16 were male patients and 15 were female patients, with 19 left and 12 right eyes. Mean age at operation was 62.0 ± 9.4 years. Mean reduction in density of the anterior 120 μm of cornea was -3.07 [95% confidence interval (CI), -6.600 to 0.460] and -3.455 (95% CI, -6.787 to -0.122) at postoperative 4 and 12 weeks, respectively, and mean reduction percentage was -4.7% (95% CI, -10.7% to 1.3%) and -6.3% (95% CI, -11.8% to -0.7%), respectively. No steroid response or pterygium recurrence was reported., Conclusions: Corneal densitometry is an objective measure to detect scar changes in zones and layers. The overall reduction of density was evident at 12 weeks postoperatively. These results might serve as baseline figures for future studies in assessing modulation of corneal scars over time.

Objective: To compare the long-term outcome of pterygium surgery and the long-term effect on endothelial counts after mitomycin C (MMC) or limbal conjunctival autograft (LCAU) in pterygium surgery., Design: We performed a 10-year follow-up study of a randomized controlled trial., Participants: A total of 115 eyes of 114 patients with primary pterygium were treated with intraoperative MMC (n = 63) or LCAU transplants (n = 52). A total of 76 patients completed the current 10-year long-term follow-up (47 in the MMC group, 29 in the LCAU group)., Methods: This is a follow-up study of a randomized controlled trial of a cohort of 114 patients in 2 groups that was performed at the Prince of Wales Hospital 10 years ago: group 1, intraoperative 0.02% MMC for 5 minutes; group 2, LCAU. Consecutive patients enrolled in the original study (recruitment began in February 2001) were invited back for a detailed clinical examination to document the long-term outcome of both surgical groups., Main Outcome Measures: The main outcome measures included the recurrence rate, residual conjunctival bed status, complications, and corneal endothelial cell density (ECD) differences., Results: A total of 115 eyes of 114 patients were enrolled and randomized in our previous study. For the current study, 76 of the 114 patients (47 in the MMC group, 29 in the LCAU group) were contacted, whereas 18 patients were lost to follow-up and 20 patients had died. The mean follow-up period was 138 ± 2 months in the MMC group and 137 ± 2 months in the LCAU group. Twelve of 47 patients (25.5%) in the original MMC group and 2 of 29 patients (6.9%) in the LCAU group had recurrent pterygium (P = 0.021). The mean ECD was 2,39 2 ± 342 cells/mm(2) in the MMC group and 2,390 ± 388 cells/mm(2) in the LCAU group (P = 0.978). There was no significant difference in the ECD between the operated eyes and the fellow eyes in both groups (P = 0.926 MMC, P = 0.468 LCAU). No other significant ocular complications were observed in either group at the 10-year postoperative follow-up., Conclusions: Limbal conjunctival autograft was more effective than intraoperative MMC in minimizing pterygium recurrence at the 10-year follow-up. Treatment with intraoperative MMC was not associated with long-term corneal endothelial cell loss., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To determine the effectiveness of lidocaine 2% gel vstetracaine 1% drops in primary pterygium surgery., Methods: This was a prospective, randomised controlled trial. Forty consecutive patients who had primary pterygium underwent surgical excision of primary pterygium and mitomycin C. Patients were randomised into two groups. Group 1 received tetracaine 1% drops and solcoseryl eye gel (Solco Basel AG, Switzerland). Group 2 received xylocaine 2% gel (lidocaine hydrochloride 2% gel, AstraZeneca, Sweden) topically and normal saline drops 0.9%. Additional tetracaine drops were given to patients who experienced pain preoperatively. The primary outcome was the pain experienced during and after surgery. Immediately after the operation, pain and discomfort scores were assessed by the patients and doctor using a 10-point linear analogue scale. The stages of the operation were divided into the following: stage 1-first incision, stage 2-pterygium body excision, stage 3-conjunctival suturing, and stage 4-immediate postoperative after patching., Results: There was no statistically significant difference in the mean pain scores experienced during pterygium excision (3.03+/-2.35 for the lidocaine group and 3.98+/-2.18 for the tetracaine group). However, for stage 3, there was a statistically significant difference in mean pain scores experienced during closure (P=0.03) (0.47+/-0.84 for the lidocaine gel group and 1.43+/-1.66 for the tetracaine group), with patients of group 2 experienced less pain. The mean number of additional drops required by the eyes in lidocaine gel group was also significantly (0.16+/-0.11) less than the tetracaine group (0.67+/-0.09, P=0.001)., Conclusions: Topical administration of lidocaine 2% gel or tetracaine 1 % drops are both effective anaesthetic agents for primary pterygium surgery and mitomycin C. However, lidocaine gel is superior to tetracaine eye drops and its application is more convenient with a less frequent application and a sustained duration of action.

Purpose: To describe the novel use of combined conjunctival rotational autograft (CRA) and intraoperative 0.02% mitomycin C (MMC) in the treatment of primary pterygium and to evaluate its safety and efficacy., Methods: Prospective interventional case series comparing with historical controls was conducted. Patients with primary pterygium underwent pterygium excision, MMC was applied to the scleral bed after the surface conjunctiva was harvested, and the CRA was sutured back with a 180-degree rotation. Patients were followed for a minimum of 1 year., Results: Sixty-seven eyes from 67 patients participated in the study, of which 31 (46.3%) were men and 36 (53.7%) were women. The mean age was 58 +/- 10.6 years, (range 36-79 years). There were 2 recurrences (3%), one occurring at month 3 and the other at month 9. Compared with historical controls, CRA-MMC resulted in significantly fewer recurrences than MMC alone (P = 0.005) when adjusted for age and was equally effective when compared with limbal-conjunctival autografts. The main postoperative problem was graft injection, which was noted in 41 eyes (61%) at 1 year., Conclusions: To the best of our knowledge, this was the first study on the combined use of CRA and MMC in the treatment of primary pterygium. CRA with MMC was found to be effective in the prevention of recurrence. Although injection remained as a cosmetic concern, it was a safe alternative to limbal-conjunctival autograft in cases where mobilizing autologous conjunctival tissue would not be feasible.

Background: Mitomycin C (MMC) and limbal conjunctival autograft (LCAU) are two known useful adjuvants in the prevention of pterygial recurrence. This study was conducted to compare the outcome of these two treatments., Methods: Prospective study on consecutive cases of primary pterygium (February 2001 to March 2002) randomised into two adjuvant groups: (1) intraoperative 0.02% MMC for 5 minutes or (2) LCAU. Patients were followed for recurrence (defined as fibrovascular tissue invading the cornea >1.5mm) and complications for a period of one year., Results: 115 eyes in 114 patients who completed the study were randomised to receive MMC (n = 63) and LCAU (n = 52). There were 10 recurrences (15.9%) in the MMC group and only one recurrence (1.9%) in the LCAU group. There was a statistically significant difference in the recurrence rate between the two groups (p = 0.04). There were a total of three conjunctival cysts, three symblephara, one granuloma, and one dellen. No other visually significant complications were encountered in either group., Conclusion: Although LCAU resulted in better one year success rates, it is technically more difficult and inapplicable in cases with previous limbal disturbance. Simple excision followed by MMC or LCAU are both safe and acceptable adjuvants for pterygium excision. Choice of adjuvant should be carefully made based on assessment of recurrence risk, local practices, and surgeon's expertise.